The overall objective of this project is the in-vivo study of the receptor or receptors involved in the actions of morphine and related compounds with the aim of differentiating and categorizing the receptors involved. Our emphasis will be with pharmacological profiles obtained from dose-response curves utilizing seizure threshold, change in pupil area, body heat flux, and analgesia as measures. Thus, we will not only make qualitative comparisons, but we will use the slopes of the dose-response curves and the shifts obtained in the presence of antagonists to make quantitative comparisons. Curves will be constructed for morphine, certain prototype analgesics, and endogenous opiate-like peptides in both naive and morphine-tolerant/dependent rats. We will also determine whether such factors as brain lesions or interactions with other drugs of abuse, which affect any one of the several endpoints, will similarly affect the others. The information to be gained is useful both as a supplement to that derived from tissue binding studies as well as for its own sake in classifying central opiate receptors. These studies should allow for a rational estimate of the possibility of separating unwanted side effects from the desirable actions of these drugs.